|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|Diseases [C] - Nervous System Diseases [C10]
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|With this study we aim to prove that personalized B cell tailored ocrelizumab treatment is non-inferior in the suppression of MS disease activity compared to the standard (fixed 24 week interval) treatment.
|Secondary objectives of the trial
|With this study we aim to prove that personalized B cell tailored ocrelizumab treatment is non-inferior in the suppression of disability and brain atrophy.
|Trial contains a sub-study
|Principal inclusion criteria
|In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• A current diagnosis of relapsing remitting multiple sclerosis according
to the 2017 McDonald criteria34
• Age of 18 or older
• EDSS score of 0 to 6.5 inclusive
• Treatment with ocrelizumab for a minimum of 48 weeks (two 300 mg infusions and one 600 mg infusion)
• Last ocrelizumab interval not extended, maximum of 7,5 months between the infusions
|Principal exclusion criteria
|A potential subject who meets any of the following criteria will be excluded from participation in this study:
• Previous treatment with alemtuzumab, cladribine or stem cell transplantation
• Relapse in the past 3 months prior to inclusion
• Subsequent treatment with another DMT next to ocrelizumab in the past 6 months prior to inclusion
• Inability to undergo regular MRI scanning
• Women who are pregnant or expect to become pregnant during the study period
|E.5 End points
|Primary end point(s)
|The two co-primary end points are the difference of percentage of confirmed relapse-free patients between the two treatment groups after 96 weeks follow-up and the difference of percentage of patients without new/enlarging T2 MRI lesions between the two treatment groups after 96 weeks follow-up.
|Timepoint(s) of evaluation of this end point
|Secondary end point(s)
|• Number of total relapses and annualized relapse rate calculated as the total number of relapses per patient divided by years of follow-up.
• Total number of active (new and/or enlarging) T2 lesions on brain MRI at 96 weeks in comparison to the baseline MRI and number of active MRI scans.
• Proportion of patients with six month confirmed disability progression on the EDSS at 96 weeks of the two treatment groups. Disability progression is defined as an increase of 1.5 points for a
baseline EDSS of 0, an increase of 1 point for baseline EDSS of 1–5.5, and an increase of 0.5 for baseline EDSS >5.5.
• Change of MSFC (T25FW, 9HPT and SDMT).
• Change of disability measured by two digital apps (MS sherpa and neurokeys)
• Rate of brain atrophy comparing baseline MRI and MRI at 96 weeks.
• Change of different subsets of the MSFC from baseline to week 96.
• Proportion of patients with NEDA at 96 weeks. NEDA is defined as absence of confirmed relapses, MRI disease activity (new/enlarging T2
lesions) and confirmed disability progression.
• Change of serum neurofilament light from baseline to highest level during the study.
• Change of quality of life measured by the SF-36 and MSIS-29.
• Change of burden of treatment measured by the TSQM.
• Presence of a possible wearing-off effect measured by a questionnaire developed by the Amsterdam MS Center.
• Change of IgG levels.
• Number of adverse and serious adverse events including infections (and COVID-19) at 96 weeks.
Tertiary research questions
When subjects participate in the data collection via the apps Neurokeys and MS Sherpa:
- To examine which Neurokeys features are associated with disease status and disease progression
- To examine which features of MS Sherpa are associated with disease status and disease progression
|Timepoint(s) of evaluation of this end point
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Standard intervals of ocrelizumab (24 weeks)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days